Nitriles are important and extremely versatile intermediates in organic synthesis. This compound class exhibits a high reactivity of the C,N triple bond, which enables numerous addition reactions. The significance in modern organic synthesis is restricted only by limitations of the availability of these compound classes.
Standard processes for preparing nitrites are eliminations of correspondingly functionalized aldoximes. Numerous methods, including those using acetic anhydride, acetyl chloride, thionyl chloride or lead oxide, are used. Other water-eliminating agents used have been phosphorus pentoxide, benzenesulfonyl chloride, ethyl chloroformate or aqueous alkalis. Thermal elimination at 340-360° C. over a metal oxide catalyst is likewise possible. One-pot processes starting from aldehydes also find use. However, it is always necessary to work at 70-140° C. The conversion of aldehydes using hydroxylamine hydrochloride and trifluoroacetic anhydride takes place at 20° C. Another variant is the reaction of aldehydes with hydroxylamine hydrochloride in pyridine/water in the presence of dicyclohexylcarbodiimide, Cu(II) salt and triethyl-amine. In addition to heavy metal salts, dicyclohexyl-urea which is removable only with extreme difficulty is also obtained.
In modern organic synthesis, the significance of chemo-, regio- and stereoselective reagents is increasing explosively. When, for example, the intention is to convert an oxime to a nitrile in a complex molecule with numerous functional groups, numerous methods of those mentioned are ruled out for selectivity reasons. The use of thermal dehydration is also restricted, since very high temperatures of up to 450° C. are required.
A selective and preferred method for eliminating oximes to nitrites is the reaction with a multitude of dehydrating agents.
There has to date been a lack of a highly selective solution to the problem of the transformations mentioned. Although the known reagents can accomplish the desired transformations, other moieties are often likewise influenced. In many cases, the drastic conditions required epimerize even far-removed stereocenters. In addition, the transformation should therefore be usable under very mild conditions, and particularly the removal of the conversion products of the reagent used should be very simple.
It is therefore an object of the invention to provide an economically viable process which allows the conversion of oximes to the corresponding nitrites by elimination of water, but at the same time permits the use of very mild reaction conditions and has a simplified workup.
The processes for preparing nitrites known in the prior art all have serious disadvantages:
For instance, when thionyl chloride is used, the reaction has to be performed at elevated temperature. This is disadvantageous in the case of sensitive compounds in particular. When lead oxide is used, the heavy metal is obtained in the waste stream.
Although the Voswinkel process has been found to be useful in the one-stage preparation of nitrites starting from aldehydes, the use of dicyclohexylcarbo-diimide harbors disadvantages since it is sensitizing, and it is often not possible to completely remove the reaction by-products.